Oral immunotherapy in hen’s egg‐allergic children increases a hypo‐proliferative subset of CD4+ T cells that could constitute a marker of tolerance achievement

Background: Food allergy affects a significant number of children and its prevalence, and persistence is undergoing an important increase in the last years. Specific oral tolerance induction (SOTI) is a promising therapy for food allergy. However, little is known about the immune mechanisms implicated in the desensitization to allergens. Our purpose was to study which immune parameters are modified during the process of tolerance achievement with the goal of identifying markers of tolerance induction. Methods: We performed an extensive immune analysis in 19 allergic children following SOTI with hen’s egg before and after the immunotherapy. Changes in lymphocyte subpopulations and serum cytokines were identified in children with desensitization achievement. Results: Sixteen children achieved complete tolerance to egg, and the immune analysis reveals that desensitization was accompanied in all the cases by a significant decrease in the percentage and absolute counts of effector‐memory CD4+ T cells (T_EM) and a marked increase in the absolute counts of a subset of CD4⁺CD38⁺CD45RO^? cells. Additionally, we also observed a marked reduction in the plasma levels of different Th1 and Th2 cytokines after tolerance achievement. Conclusions: Acquisition of tolerance in children after oral immunotherapy is accompanied by a decrease in the T_EM population and the increase in a particular subset of CD4+ T cells with a hypo‐proliferative and non‐reactive phenotype. This hypo‐proliferative subset of cells could constitute a marker of the development of oral tolerance, and the study of this subset could contribute to the better understanding of the immune responses in allergic subjects.